Synthesis of diacetyl-3, 3-diamino-4, 4&#39;-dikydroxy-5, 5-diiodoarsenobenzene



Patented Nov. 25, 1930 ALExannEn Donates MAoALLu a; creates new; new s-may I SYNTHESIS on niAoETYL-wDiamante-a i n No Drawing. Application filed Ma ches, 1928, seriaritm eeaiao, an; meme ixmsmmayg 1927.

Although iodides and certainorganic. iodine derivatlves have had medlcal application in conjunction withthe aromatic arseno compounds, eitortsto combine the effects of the two by introductionof nuclear halogen into the arsenical's themselves have not heretofore been successful. otherwise, possibly;

than inthe case ofbismethylamino-tetramlnoarsenobenzene (Kolle Deutsche Medllozinische Wochenschritt, 44, 11-?7 (1918);

Giemsa: same, 45, 95 (1919)).

This patent application concerns the synthesis of another efii'ective aromatic arsenical containing nuclear halogen, diacetyl-3,3-di

amino-4 F- dihydroxy 5,5- diiodoarsenoben-.

zene (IV) solutions of which are remarkably stable. The drug produces no undesirable nervous eflects, is generally welltolerated by mice and has at the same time a strong trypanocida-l action.

The foregoing arseno-compound (IV) is produced by reduction of acetyl-3-amino4l--' hydroxy-5 iodophenylarsonic acid (III),

' which in turn is prepared by reduction of 8- nitro 4-hydroxy-5-iodophenylarsonic acid (1) to 3-amino-4-hydroxy-5-iodophen.ylarsonic acid (H) and by subsequent acetylation of the amino-acid.

The four compounds, of which (I), the

i nitro-acid, is well known (Rai'ziss, Kolmer,

and Gavron: J. Biol. Chem 40, 541 (1919) Stieglitz, Kharasch, and Hanks; J. Amer.-

Chem. Soc., 43, 1192 (1921)) are formulated as follows: 1

AS03111 AS03132 AS03112 pounds. The reduction may suitably be car- Nuoooni 1 Beduction of the nitro-acid (I) to the at amino-acid (II) can be effected in cold. alkaline solution eaii i by an jexcess of freshlyprecipitated.titanous or terrous oxide or by useof sodiumhydrosulphitef I snnexrtj"rnIronoARsENoBnnzENEL To obtainthe acetylalmino-acid,(IID'Qt'hd reduction mixture in the first casenisdi'eed from iron or 'titaniumfoxides'by filtration, the filtrate neutral zedwith acetic acid, and

then treated underacoolinglwith an excess of acetic anhydride. The acetyl; compound crystallizes out after a time.

"The procedure is moredirect Where hydrosulphite has been used forthe reduction, as in the following example.

Acetyl-fi-amino -hg dromy-iodogihehg/Z- arsenic (we'd (1H A solution of 3.9 of,

the nitro-acid (1) in 40480 cc. of water and 2 cc. of lO-N alkali is treated at 0 with suflicient hydrosulphite powder (68 g.) to bleach it. Acetic; anhydride is now added at intervals in several portions of 1 cc. After 28 hours most of the acetyl derivative will have separated. and the sulphite may then be destroyed by the gradual addition of 50-60 cc. of hydrogen peroxide (or until a drep of the solution no longer decolourizes potassium"triiodide), the solution being kept nearly neutral by suitable additlons of sodium bicarbonate.

Finally, the

wholeo-f the acetyl compound is precipitated (yield, 2.99 g; 74%) by making the solution just acid to Congo paper.

The washed and dried product formsa cake of colourless needles, m. p. 158159, v

readily soluble in the alcohols and acetone.

By recrystallization from dilute aceticacid (1:1), the acetyl compound is obtained in prisms, m. p. 190-191 The two forms of acetylamino-acid lead on reduction to what appear to be (from mixed melting points) identical arseno comried out as follows dz'iodoarsenobenzene (IV) .-A solution of 2.7. g. of the'preceding acetyl compound (either form) in 100 cc. of Water containing 3 g. of sodium bicarbonate is warmed at 55'60 with 15 g. of hydrosulphite in an atmosphere of nitrogen for 1"5 hours. The

arseno compound separating forms, after washing and drying in a Vacuum, a lemonyellow powder (yield 1.66 g.; 70%), m. p. 194: after sintering at about 180.

It is soluble in acetone, phenol, benzaldehyde, or pyridine, and its dilute solutions in alkali carbonates or hydroxides undergo little apparent change on exposure'to the air.

What I claim is:

1. A process for synthesis of diacetyl-3,3- diamino- 4A? dihydroxy 5,5 diiodoarsenobenzene which consists in warming together, in an indifferent atmosphere, substantially neutral solutions of acetyl-3-amino-4-hydroxy-5-iodophenylarsonic acid and sodium hydrosulphite, suitably at 55-60".

2. As a new product, diacetyl-3,3-diamino- 4A dihydroxy 5,5 diiodoarsenobenzene, said product being a lemon-yellow solid soluble in acetone, phenol, bcnzaldehyde and pyridine.

fill

Signed at Perth Amboy, N. J U. S. A., this 20th day of March, 1928.

ALEXANDER DOUGLAS MACALLUM. 

